A case report of CIC–DUX4 fusion-positive sarcoma in the pelvic cavity with targeted next-generation sequencing results

Abstract

CIC–DUX4 fusion-positive sarcoma is a subtype of undifferentiated small round cell sarcoma that is rarely reported. As far as we know, less than 200 cases have been reported worldwide to date. The clinicopathologic characteristics of this kind of tumor are non-specific, which makes it difficult to be diagnosed. Therefore, more cases are required to enrich the diagnosis and treatment experience. Here, we present a 17-year-old Asian girl diagnosed with CIC–DUX4 fusion-positive sarcoma after targeted next-generation sequencing. Her clinical manifestation was abdominal pain. Furthermore, a mass in the pelvic cavity and massive ascites were found after an imaging examination. After resection, the mass was sent to the pathology department for a definite diagnosis, and the micromorphology showed an undifferentiated sarcoma with massive necrosis. The tumor cells were round to spindle with clear to eosinophilic cytoplasm and vesicular nuclei. Rhabdoid cells and myxoid mesenchyme were focally shown. Immunohistochemical staining showed diffusely positive for vimentin, cyclin D1, Fli-1, and WT-1 and very focally positive for CD99. Moreover, the targeted next-generation sequencing also revealed other genetic changes in this tumor including LongInDel of POLE, copy number variation of CD79, low tumor mutational burden, and microsatellite stability. With a follow-up time of 6 months, the patient survived the disease and received chemotherapy routinely. This report presented a rare primary site CIC–DUX4 fusion-positive sarcoma (CDS) and revealed novel genetic changes that enrich the manifestation, histology, and cytogenetic scales of this rare sarcoma. In addition, we have summarized the clinicopathologic characteristics of this tumor by reviewing the literature to have a better understanding of CIC–DUX4 fusion-positive sarcomas, which may be helpful for diagnosis and treatment.

Molecular and therapeutic advancements in Capicua (CIC)-rearranged sarcoma

“…In our series of CIC::DUX4 confirmed case reports median age of CDS diagnosis was 29.5 years old with a range from 11 to 82 years old and a male-to-female ratio of fourteen to eighteen (Machado et al, 2013;Bielle et al, 2014;Kajtár et al, 2014;Haidar et al, 2015;Tardío et al, 2015;Chebib and Jo, 2016;Bergerat et al, 2017;Krskova et al, 2017;Loke et al, 2017;Tsukamoto et al, 2017;Camille et al, 2018;Donahue et al, 2018;Mangray et al, 2018;Tang and Dodd, 2018;Lehane et al, 2019;Maloney et al, 2020;Ricker et al, 2020;Tamada et al, 2020;Yamada et al, 2020;Chen et al, 2021;Maejima et al, 2021;Maekawa et al, 2021;Vieira et al, 2021;Wu and He, 2022;Aranza et al, 2023;Ascione et al, 2023;Wu et al, 2023) (Table 1). Within the thirty-two CDS patients that we analyzed through case studies, ten tumors localized primarily in the soft tissue of lower extremities, with a significant fraction also presenting in the soft tissue of the upper extremities and kidney as well as pelvic cavity area.…”

“…Of the four CIC-rearranged sarcomas, summary statistics of the available data within the case reports indicate CIC::DUX4 sarcoma to be associated with a relatively more aggressive clinical course, presenting with the highest rate of metastasis (76%; total n = 29) and a predilection for the lungs (Machado et al, 2013;Bielle et al, 2014;Kajtár et al, 2014;Haidar et al, 2015;Tardío et al, 2015;Chebib and Jo, 2016;Bergerat et al, 2017;Krskova et al, 2017;Loke et al, 2017;Tsukamoto et al, 2017;Camille et al, 2018;Donahue et al, 2018;Mangray et al, 2018;Tang and Dodd, 2018;Lehane et al, 2019;Maloney et al, 2020;Ricker et al, 2020;Tamada et al, 2020;Yamada et al, 2020;Chen et al, 2021;Maejima et al, 2021;Maekawa et al, 2021;Vieira et al, 2021;Wu and He, 2022;Aranza et al, 2023;Ascione et al, 2023;Wu et al, 2023). Sarcoma patients harboring the CIC::FOXO4 fusion also had a high rate of pulmonary metastasis (75%; total n = 4), while patients with the CIC::NUTM1 tumors had the lowest overall rate of metastasis (25%; total n = 12) with distant sites including the lungs, thyroid, bone, and brain (Solomon et al, 2014;Sugita et al, 2014;Mangray et al, 2018;Schaefer et al, 2018;Le Loarer et al, 2019;Biederman et al, 2022;Connolly et al, 2022;Yang et al, 2022;Babkoff et al, 2023;Ma et al, 2023;…”